B. Sloane
Bonnie F. Sloane, Ph.D.
Distinguished Professor and Chair

Department of Pharmacology,
Wayne State University School of Medicine and
Distinguished Professor, Karmanos Cancer Institute

Adjunct Professor, Department of Biological Sciences, University of Windsor, Ontario, Canada

540 E. Canfield
Detroit MI 48201

Tel: (313) 577-1580
Lab: (313) 577-1112 
FAX: (313) 577-6739
E-mail: bsloane@med.wayne.edu
RESEARCH INTERESTS:

Dr. Sloane’s laboratory has a longstanding interest in the roles of proteases in development and progression of cancer.  Their primary emphasis is proteolytic pathways in tumors and their cellular microenvironment in the progression of premalignant breast disease to invasive carcinomas.  Her research group has established a role for lysosomal proteases, primarily the cysteine protease cathepsin B, and the endogenous inhibitors of cysteine cathepsins (the cystatins and stefins) in malignant progression.  They were the first group to uncover molecular mechanisms for the increased expression of cathepsin B in human tumors and to identify binding partners responsible for alterations in localization of cathepsin B in tumors.  This includes the association of cathepsin B with caveolae on the cell surface via the direct binding of procathepsin B to S100A10, p11 or the light chain of the annexin II heterotetramer, in complex with the heavy chain annexin II.  They have confirmed this association in a number of types of tumors, including inflammatory breast cancer (IBC).  IBC is a highly malignant cancer that disproportionately affects young women, occurring more frequently in women of North African and African-American origin and thus important to our local Detroit community.  Further studies on IBC, proteases and lymphangiogenesis are ongoing in our laboratory and with Dr. Cavallo-Medved at the University of Windsor and Dr. Mostafa Mohamed at Cairo University. 

The Sloane group has been a leader in applying live-cell imaging to the protease field, in our case to the study of proteases in breast cancer.  Our impetus for so doing is the need to study protease activity and proteolytic cascades if we are to exploit the potential of proteases as biomarkers, therapeutic targets or surrogate endpoints.  Our laboratory is currently working toward all of those goals.  For this purpose, we have established new assays to follow proteolysis by live human breast cells in real time as they form 3-dimensional structures in matrices and migrate through the matrices, thus analyzing proteolysis in four dimensions.  We have employed these assays to follow the interactions among breast tumor cells and tumor-associated cells in an effort to determine: 1) whether the various cellular components comprising a tumor use proteolysis to perform their functions (e.g., is there proteolysis associated with infiltration of fibroblasts and macrophages into tumors?  With endothelial cell migration and formation of neovessels?); 2) what are the contributions of the various cellular components to collective tumor proteolysis; and 3) what is the contribution of cell:cell interactions to collective tumor proteolysis.  We have expanded our analyses to determine how kinase pathways and cytokine/chemokine pathways intersect with and regulate proteolytic pathways and the role(s) of tumor-associated cells in these processes.  Our current work focuses on premalignant breast disease.  Via our live-cell imaging assays and novel organotypic model systems, we are defining pathways that increase or decrease the transition from a non-invasive through a pre-invasive to an invasive phenotype.  We are working to translate the imaging techniques to make treatment decisions about patients with ductal carcinomas in situ, the 4th most prevalent cancer in women in this country.

Ongoing collaborative studies, with Dr. Mattingly and Drs. Haywood and Matrisian of Vanderbilt University, are directed toward defining proteolytic pathways and their intersections with kinase and chemokine/cytokine pathways in tumors and the tumor microenvironment.  The goal of these studies is to identify mechanisms by which the tumor microenvironment alters proteolysis in order to design therapeutic strategies to target interactions between the tumor and its microenvironment.

Current Lab Personnel

Some Lab Alumni

Current Collaborators

Selected Recent Publications

Links:

http://www.protease.org/
http://cdmrp.army.mil/bcrp/coeawards.htm
Avon Foundation International Scholars in Training         
http://www.burnham.org/default.asp?contentID=81
http://nihroadmap.nih.gov/buildingblocks/technologycenters/
http://bioweb2.bio.uea.ac.uk/cancerdegradome/welcome.html
http://www.med.wayne.edu/mirl/
http://www.karmanos.org
http://www.iehs.wayne.edu/ehs_center.html
http://www.ssim.eng.wayne.edu/
The cancer degradome
ASMR 2008